Search

Cytomegalovirus (CMV) commonly infects immunocompromised individuals, such as cancer patients. We present a case involving a 60‐year‐old male with Stage 3A lung adenocarcinoma and chronic obstructive pulmonary disease (COPD) diagnosed with CMV tracheobronchitis, initially suspected as cancer progression. Treatment with ganciclovir led to partial improvement in symptoms of shortness of breath and cough, as well as bronchoscopic findings. However, due to ganciclovir‐induced neutropenia, the therapy was switched to foscarnet. Distinguishing between cancer progression and infectious tracheobronchitis through physical examination and chest CT scans remains challenging. In lung cancer patients presenting with airway and bronchial narrowing along with ulcerative mucosal lesions, CMV infection should be considered. A bronchoscopic biopsy is crucial for accurate diagnosis and determining the appropriate treatment in these patients. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) chronic retinal necrosis (CRN) is a rare viral retinal infection that occurs in mildly immunocompromised people. It shares some features with both acute retinal necrosis and CMV retinitis. It is typically treated with combination intravitreal and systemic ganciclovir. We discuss the management of a case of CMV CRN with ganciclovir resistance. Case presentation: An 80-year-old female presented with one month of blurry vision in the left eye. She was being treated with abatacept, methotrexate, and prednisone for rheumatoid arthritis. Examination revealed anterior chamber and vitreous cell along with peripheral retinal whitening. Fluorescein angiogram showed diffuse retinal non-perfusion. Aqueous fluid PCR testing returned positive for CMV. The retinitis was initially controlled with oral and intravitreal ganciclovir, but then recurred and progressed despite these therapies. Ganciclovir resistance was suspected and the patient was switched to intravitreal foscarnet injections, along with oral letermovir and leflunomide, which lead to resolution of the retinitis. The patient has now continued with letermovir and leflunomide for approximately 2.5 years without reactivation of the retinitis or need for further intravitreal anti-viral injections and with adequate control of her rheumatoid arthritis. Conclusion: The incidence of CMV CRN may increase in the future as the use of non-cytotoxic immunosuppressive therapies that result in relatively mild immunosuppression also increases. Treatment with ganciclovir is effective but frequently leads to resistance, as in our case. In this situation, combination therapy with letermovir and leflunomide, particularly in the setting of rheumatoid arthritis where leflunomide can also have an anti-inflammatory effect, can be considered. [ABSTRACT FROM AUTHOR]

Congenital cytomegalovirus (cCMV) is the most common cause of congenital infection and the leading cause of non-genetic sensorineural hearing loss in childhood. While treatment trials have been conducted in symptomatic children, defining asymptomatic infection can be complex. We performed a scoping review to understand how infection severity is defined and treated globally, as well as the various indications for initiating treatment. We conducted an electronic search of MEDLINE, EMBASE, Scopus, and the Cochrane Library, using combinations of the following terms: "newborn", "baby", "child", "ganciclovir", "valganciclovir", and "cytomegalovirus" or "CMV". We included eligible prospective and retrospective studies, case series, and randomized clinical trials (RCTs) published up to May 2024. A total of 26 studies were included, of which only 5 were RCTs. There was significant heterogeneity between studies. The most commonly considered criteria for symptomatic infection were microcephaly (23/24 studies), abnormal neuroimaging (22/24 studies), chorioretinitis/ocular impairment (21/24 studies), and hearing impairment (20/24 studies). Two studies also included asymptomatic newborns in their treatment protocols. Outcome measures varied widely, focusing either on different hearing assessments or neurocognitive issues. Our literature analysis revealed significant variability and heterogeneity in the definition of symptomatic cCMV infection and, consequently, in treatment approaches. A consensus on core outcomes and well-conducted RCTs are needed to establish treatment protocols for specific groups of newborns with varying manifestations of cCMV. [ABSTRACT FROM AUTHOR]

A novel, environment friendly high-performance liquid chromatography method for the determination of Ganciclovir in drug and formulations. Current HPLC methods often rely on acetonitrile, a solvent known to pose environmental and health hazards. Despite extensive literature review ganciclovir was estimated using only traditional HPLC solvents no studies were reported using ethanol. The developed method utilizes a simple mobile phase consisting of ethanol and acidic water (pH 3.0) at an optimized ratio of 80:20 v/v. Separation is achieved on a Zorbax eclipse plus C18 column (4.6 × 150 mm, 5 μm) with a flow rate of 1.0 mL/min. The proposed method demonstrates excellent linearity, and precision, assessed by (r2 ≥ 0.999) and %RSD by below 2%, with recovery 98–102%. The method's greenness was evaluated using established assessment tools such as AGREE, GAPI, and COMPLEX GAPI confirming the method's adherence to 12 green analytical principles. The proposed method's capability of separation from degradation products and no significant change of peak area and retention time was observed. This study explores the feasibility of substituting the acetonitrile with an eco-friendly greener alternative, ethanol recognized for its low toxicity and environmental impact. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) retinitis is a rare disease, and overlapping manifestations involving the anterior segment are extremely uncommon. We report a patient who initially presented with persistent corneal edema and was later diagnosed with CMV retinitis. A 72-year-old man with uncontrolled intraocular pressure (IOP) in his right eye visited a tertiary hospital. At initial presentation, the IOP was 36 mmHg and the fundus was not clear due to corneal edema. Spectral domain optical coherence tomography revealed paracentral acute middle maculopathy (PAMM). Panretinal obstructive vasculopathy was observed on ultra-widefield fluorescein angiography. Three weeks later, trabeculectomy was performed to resolve the persistently high IOP. Once corneal edema improved, a white patch-like peripheral lesion and silver wire-like retinal vasculature were observed. Polymerase chain reaction of the aqueous humor was positive for CMV. Oral valganciclovir and intravitreal ganciclovir were administered as antiviral therapies. Despite treatment for 4 months, the final visual acuity was no light perception, with persistent corneal edema and neovascularization of the iris. We describe a rare case of the simultaneous occurrence of hypertensive uveitis and CMV retinitis. The presence of PAMM could be an initial identifiable sign of CMV retinitis, even in the presence of media opacity.

Abstract Cytomegalovirus (CMV) commonly infects immunocompromised individuals, such as cancer patients. We present a case involving a 60‐year‐old male with Stage 3A lung adenocarcinoma and chronic obstructive pulmonary disease (COPD) diagnosed with CMV tracheobronchitis, initially suspected as cancer progression. Treatment with ganciclovir led to partial improvement in symptoms of shortness of breath and cough, as well as bronchoscopic findings. However, due to ganciclovir‐induced neutropenia, the therapy was switched to foscarnet. Distinguishing between cancer progression and infectious tracheobronchitis through physical examination and chest CT scans remains challenging. In lung cancer patients presenting with airway and bronchial narrowing along with ulcerative mucosal lesions, CMV infection should be considered. A bronchoscopic biopsy is crucial for accurate diagnosis and determining the appropriate treatment in these patients.

Abstract Background Cytomegalovirus (CMV) chronic retinal necrosis (CRN) is a rare viral retinal infection that occurs in mildly immunocompromised people. It shares some features with both acute retinal necrosis and CMV retinitis. It is typically treated with combination intravitreal and systemic ganciclovir. We discuss the management of a case of CMV CRN with ganciclovir resistance. Case presentation An 80-year-old female presented with one month of blurry vision in the left eye. She was being treated with abatacept, methotrexate, and prednisone for rheumatoid arthritis. Examination revealed anterior chamber and vitreous cell along with peripheral retinal whitening. Fluorescein angiogram showed diffuse retinal non-perfusion. Aqueous fluid PCR testing returned positive for CMV. The retinitis was initially controlled with oral and intravitreal ganciclovir, but then recurred and progressed despite these therapies. Ganciclovir resistance was suspected and the patient was switched to intravitreal foscarnet injections, along with oral letermovir and leflunomide, which lead to resolution of the retinitis. The patient has now continued with letermovir and leflunomide for approximately 2.5 years without reactivation of the retinitis or need for further intravitreal anti-viral injections and with adequate control of her rheumatoid arthritis. Conclusion The incidence of CMV CRN may increase in the future as the use of non-cytotoxic immunosuppressive therapies that result in relatively mild immunosuppression also increases. Treatment with ganciclovir is effective but frequently leads to resistance, as in our case. In this situation, combination therapy with letermovir and leflunomide, particularly in the setting of rheumatoid arthritis where leflunomide can also have an anti-inflammatory effect, can be considered.

Raymund R Razonable1,2 1Division of Public Health, Infectious Diseases and Occupational Medicine, Mayo Clinic, Rochester, MN, USA; 2William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, USACorrespondence: Raymund R Razonable, Email razonable.raymund@mayo.eduAbstract: Cytomegalovirus (CMV) infection is arguably the most important infectious complication that negatively affects the outcome of solid organ transplantation. For decades, CMV management after transplantation has relied on antiviral drugs that inhibit viral DNA polymerase (ganciclovir, foscarnet, and cidofovir). However, their use has been complicated by myelosuppression, nephrotoxicity, and selection of drug-resistant viruses. During the past few years, the therapeutic armamentarium for the management of CMV in solid organ transplant recipients has expanded with the approval of letermovir for CMV prophylaxis in high-risk CMV D+/R- kidney recipients, and maribavir for the treatment of refractory and resistant CMV infection. Both drugs offer significant improvement when compared to standard anti-CMV therapies; letermovir was as efficacious for CMV prevention, whereas maribavir was more effective in treating refractory and resistant CMV infections. Both letermovir and maribavir have favorable safety profiles compared to CMV DNA polymerase inhibitors, without the risk of neutropenia and leukopenia associated with ganciclovir and renal toxicities associated with foscarnet and cidofovir. Moreover, letermovir and maribavir are orally bioavailable, which allows convenient outpatient treatment. However, letermovir and maribavir have a significant drug interaction potential in solid organ transplant recipients, resulting in higher levels of calcineurin inhibitors (cyclosporine and tacrolimus) and mTOR inhibitors (sirolimus and everolimus). Both letermovir and maribavir are CMV-specific and do not have clinical efficacy against other herpes viruses. Thus, there is a need for additional antiviral drugs to prevent herpes simplex and other herpes viruses when clinically indicated. This article provides a comprehensive review of the clinical data supporting the use of letermovir and maribavir in clinical practice. The author provides perspectives on the role of these newly approved drugs in the current management landscape of CMV infection in solid organ transplantation.Keywords: cytomegalovirus, maribavir, letermovir, ganciclovir, drug resistance, prophylaxis, treatment

A regioselective novel one-pot synthesis of heterocyclic purine derivative antiviral agent Ganciclovir in which initially guanine is treated with acetic anhydride in the presence of iodine (5%) to get diacetyl guanine intermediate, which undergoes in situ N-alkylation with AMDP in presence of catalytic acidic Amberlite IR-120 to get N-alkylated intermediate and finally deacetylation to get pure regioselective Ganciclovir, which is commercially viable and eco-friendly. We developed one-pot synthesis of antiviral drug Ganciclovir. Initially, Guanine is treated with acetic anhydride and iodine to yield diacetyl guanine 3. This intermediate then reacted with AMDP in the presence of acidic Amberlite IR-120 to obtain compound 5. Finally, deacetylation yields Ganciclovir 1, a commercially viable and eco-friendly process. [ABSTRACT FROM AUTHOR]

Abstract The prevention and treatment of many herpesvirus associated diseases is based on the utilization of antiviral therapies, however therapeutic success is limited by the development of drug resistance. Currently no single database cataloguing resistance mutations exists, which hampers the use of sequence data for patient management. We therefore developed HerpesDRG, a drug resistance mutation database that incorporates all the known resistance genes and current treatment options, built from a systematic review of available genotype to phenotype literature. The database is released along with an R package that provides a simple approach to resistance variant annotation and clinical implication analysis from common sanger and next generation sequencing data. This represents the first openly available and community maintainable database of drug resistance mutations for the human herpesviruses (HHV), developed for the community of researchers and clinicians tackling HHV drug resistance.

The prevention and treatment of many herpesvirus associated diseases is based on the utilization of antiviral therapies, however therapeutic success is limited by the development of drug resistance. Currently no single database cataloguing resistance mutations exists, which hampers the use of sequence data for patient management. We therefore developed HerpesDRG, a drug resistance mutation database that incorporates all the known resistance genes and current treatment options, built from a systematic review of available genotype to phenotype literature. The database is released along with an R package that provides a simple approach to resistance variant annotation and clinical implication analysis from common sanger and next generation sequencing data. This represents the first openly available and community maintainable database of drug resistance mutations for the human herpesviruses (HHV), developed for the community of researchers and clinicians tackling HHV drug resistance. [ABSTRACT FROM AUTHOR]

AbstractGanciclovir, a guanine analogue, is used intravenously (IV) first-line for the prophylaxis and treatment of cytomegalovirus (CMV) infection in solid organ transplant recipients. The pharmacokinetics (PK) of ganciclovir are highly variable, with myelosuppression occurring at high concentrations. Ganciclovir is primarily renally excreted as the parent compound, and clearance is significantly reduced in renal impairment. Acute kidney injury (AKI) is a common post-operative complication of cardiac transplantation, reducing the clearance of ganciclovir. In the intensive care unit (ICU), AKI is often managed by kidney replacement therapy (KRT). One form of KRT, prolonged intermittent kidney replacement therapy (PIKRT) is increasingly used for cost and flexibility advantages. Ganciclovir dosing recommendations are available for varying degrees of renal impairment and KRT, except for PIKRT. In this case of cardiac transplantation, complicated by anuric AKI, a ganciclovir dose of 2.0–2.5 mg/kg of adjusted body weight given after each PIKRT session was demonstrated to achieve PK targets. [ABSTRACT FROM AUTHOR]

Ganciclovir (GCV) and its prodrug valganciclovir (VGCV) are antiviral medications primarily used to treat infections caused by cytomegalovirus (CMV), particularly in immunocompromised individuals such as solid organ transplant (SOT) recipients. Therapy with GCV is associated with significant side effects, including bone marrow suppression. Therefore, therapeutic drug monitoring (TDM) is mandatory for an appropriate balance between subtherapeutic and toxic drug levels. This study aimed to develop and validate three novel methods based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for GCV determination in serum (reference methodology), dried serum spots (DSS), and VAMS-Mitra™ devices. The methods were optimized and validated in the 0.1–25 mg/L calibration range. The obtained results fulfilled the EMA acceptance criteria for bioanalytical method validation. Assessment of DSS and VAMS techniques extended GCV stability to serum for up to a minimum of 49 days (at room temperature, with desiccant). Developed methods were effectively evaluated using 80 clinical serum samples from pediatric renal transplant recipients. Obtained samples were used for DSS, and dried serum VAMS samples were manually generated in the laboratory. The results of GCV determination using serum-, DSS- and VAMS-LC-MS/MS methods were compared using regression analysis and bias evaluation. The conducted statistical analysis confirmed the interchangeability between developed assays. The DSS and VAMS samples are more accessible and stable during storage, transport and shipment than classic serum samples. [ABSTRACT FROM AUTHOR]

Congenital cytomegalovirus (cCMV) infection is the most common cause of neurodevelopmental sequelae in the United States (US). The most common long-term disability associated with cCMV is sensorineural hearing loss (SNHL). Among children with cCMVassociated SNHL, over 40% will pass their newborn hearing screen (NHS). Therefore, to maximize the identification of infants at risk for SNHL, there is a strong rationale for universal cCMV screening. Early identification of cCMV also allows for the timely commencement of antiviral therapies for some infants, which in turn can improve clinical outcomes. Congenital infection must be diagnosed in the newborn infant in the first 21 days of life since demonstration of CMV infection beyond this time point commonly reflects postnatal acquisition, typically from breastfeeding. Although many advocates are enthusiastic about universal cCMV screening (1-3), other experts express hesitancy in embracing such a policy recommendation until there is more evidence of cost-effectiveness. Moreover, since most infants with cCMV are asymptomatic and have a good prognosis for normal neurodevelopmental outcomes, there is concern that universal screening may raise undue anxiety for parents of infants with asymptomatic cCMV infection (4). This review considers the pros and cons of different cCMV screening approaches, emphasizing enhancing awareness of new and emerging approaches for neonatologists in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of ganciclovir combined with recombinant human interferon on clinical efficacy and immune function of children with infectious mononucleosis(IM). Methods: This was a retrospective study. Children (n=120) with IM hospitalized in Beijing Children’s Hospital Affiliated to Capital Medical University Baoding Hospital from January 2020 to January 2022 were selected and randomly divided into study group and control group((n=60). Patients in the control group were treated with ganciclovir by intravenous infusion, and patients in the study group were given ganciclovir+recombinant human interferon-α1b. The time for eliminating clinical symptoms, the levels of inflammatory cytokines, immune function condition and T-lymphocyte subsets between the two groups were compared and analyzed. Results: After treatment, the time for body temperature returned to normal, time for recovery from cervical lymphadenopathy, time for recovery from hepatosplenomegaly and time for disappearance of angina and oral mucosal congestion in the study group were significantly shorter than those in the control group(p= 0.00); after treatment, the levels of TNF-a and IL-6 in the study group were significantly lower than those in the control group; the indexes of CD3+ and CD8+ in the study group were significantly lower than those in the control group; after treatment, the levels of CD4+ and CD4+ /CD8+ in the study group were significantly higher than those in the control group. Conclusion: Ranciclovir combined with recombinant human interferon-α1b, rapid improvements of clinical symptoms, significantly decreased inflammatory cytokines, improved T-lymphocyte function and no significant increase in adverse drug reactions were found in children with IM. [ABSTRACT FROM AUTHOR]

Background: Acquired human cytomegalovirus (CMV) is a noteworthy disease in infants. This case study will highlight the influence of early diagnosis of CMV retinitis (CMVR) on avoid visual impairment. Clinical Findings: We describe a preterm female infant with a birth weight of 2060 gr that was admitted for tracheostomy placement due to hypoxic-ischemic encephalopathy. There were no signs of CMV infection or sepsis in laboratory results upon admission such as serology (IgG, IgM antibodies), Toxoplasma gondii, Rubella virus, Herpes simplex virus, CMVR and urine polymerase chain reaction (PCR). Primary Diagnosis: Incidentally, upon screening for retinopathy of prematurity, diffuse occlusive vasculitis was detected in the retinal image on the 112th day of life. Intervention: Intravenous and intraocular ganciclovir were administered for 4 weeks. Outcomes: In the follow-up visit 6 weeks after discharge from the hospital, visual impairment was detected on both sides. Practice Recommendations: This is a report of a case of acquired CMVR, a silent finding, as an uncommon complication in preterm neonates during the hospital stay. This diagnosis should be taken into consideration in preterm infants, since early diagnosis and treatment are crucial to avoid visual impairment. [ABSTRACT FROM AUTHOR]

The article discusses a case of successful recovery from HHV-6 encephalitis in a 2-year-old immunocompetent child. The child presented with fever, altered sensorium, aphasia, and neck stiffness, and was diagnosed with HHV-6 encephalitis through CSF analysis and MRI. Treatment included antibiotics, antivirals, IVIG, and methylprednisolone, leading to a full recovery without neurological deficits. The article emphasizes the importance of considering viral etiology in pediatric meningoencephalitis cases and prompt treatment for positive outcomes. [Extracted from the article]

Infection management in solid organ transplantation poses unique challenges, with a diverse array of potential pathogens and associated antimicrobial therapies. With limited high-quality randomized clinical trials to direct optimal care, therapeutic "myths" may propagate and contribute to suboptimal or excessive antimicrobial use. We discuss 6 therapeutic myths with particular relevance to solid organ transplantation and provide recommendations for infectious diseases clinicians involved in the care of this high-risk population. [ABSTRACT FROM AUTHOR]

This study focused on the prevalence, unique features, and required treatment of steroid-dependent Posner-Schlossman syndrome (SD-PSS), and analyzed the outcome of 2% Ganciclovir and gradual decrement steroid combination therapy in SD-PSS patients. Retrospective comparative and interventional study. SD-PSS was defined as PSS patients with continuous steroid use for over 3 months and relapsed within 2 weeks after steroid withdrawal or tapered dosage. Totally 74 SD-PSS eyes were compared with 78 randomly chosen non-steroid dependent PSS eyes. SD-PSS patients who underwent 2% GCV and gradual decrement steroid therapy with at least two follow-ups (n = 50) were analyzed for the treatment outcome. The prevalence of SD-PSS is 26.87% (97/361) in our PSS patients. SD-PSS patients demonstrated significantly younger onset age, longer disease course, higher intraocular pressure (IOP), and higher degree of iris depigmentation at the first visit. They required significantly more IOP-lowering medication and stronger steroid after the first visit. Our 2% GCV and gradual decrement steroid therapy helped 66% (33/50) SD-PSS patients with steroid withdrawal (median stable time: 13 weeks) and another 32% (16/50) SD-PSS managed to lower the dose or strength of topical steroid. Steroid-induced ocular hypertension happened in 5.26% (19/361) of the PSS patients. Young onset age, high IOP, and high iris depigmentation level during acute stage are indicators of steroid dependency in PSS patients. SD-PSS patients require more medical surveillance. Two percent ganciclovir and gradual decrement steroid combination therapy help with steroid withdrawal and minimize steroid use. [ABSTRACT FROM AUTHOR]

Intravitreal Ganciclovir has been one of the treatments of choice for cytomegalovirus (CMV) retinitis and has been used extensively for its treatment since 1987. It has not been shown to have any major adverse effects. There are no reports on any retinal toxicity even after multiple, repeated injections. Herein, we report a rare case of retinal toxicity after multiple intravitreal injections in a patient of CMV retinitis. A 69-year-old one eyed male, who was on oral corticosteroids and systemic immunosuppression for Granulomatosis with Polyangiitis, presented with CMV retinitis in both eyes. His visual acuity was 20/60 in his right eye and no perception of light in his left eye. He was treated with multiple injections of intravitreal Ganciclovir in his right eye. The left eye was not treated since it had no vision potential. The right eye of the patient which had received multiple injections went on to developed a progressive diffuse atrophy of Retinal Pigment Epithelium (RPE). No such changes were noted in the left eye of the patient. We present a case of progressive diffuse RPE atrophy as a result of toxicity of intravitreal ganciclovir injections. It is important to be aware of this rare potential toxicity of intravitreal Ganciclovir. [ABSTRACT FROM AUTHOR]

To present the process from acute Posner-Schlossman syndrome (PSS) relapse to remission under 2% ganciclovir (GCV), corticosteroids and anti-glaucoma agents on 323 patients. A retrospective study enrolling 323 PSS patients. Demographics and ophthalmic examination results were generated. Patients were treated with GCV, corticosteroids and anti-glaucoma agents andfollowed up every 2–6 weeks. Patients were divided into the GCV monotherapy (N = 65, 20.12%), GCV and corticosteroids (G+C, N = 106) and GCV, corticosteroid and IOP-lowering drugs (G+C+L, N = 152) group. The G+C+L group had the highest intraocular pressure (IOP, 26.33 ± 10.26 mmHg, P < 0.001) and largest cup-to-disc ratio (0.58 ± 0.19, P < 0.05). After treatment, IOP of three groups dropped to similar level. Ninety-nine (30.65%) patients were corticosteroid-dependent whose daily corticosteroid consumption decreased after using GCV (from 2.23 ± 1.02 to 0.97 ± 0.98 drops/day). 2% GCV solutions worked effectively on PSS relapse with corticosteroids and anti-glaucoma agents. In patients suspected of CMV infection, proper GCV could reduce the chance of corticosteroid dependence. [ABSTRACT FROM AUTHOR]

The article offers several case studies which include the removal of a dislocated Ganciclovir implant, the role of early vitrectomy for endophthalmitis, and a case of inherited retinal disease. Topics include EURETINA's initiatives and annual congress, the ongoing debate about early vitrectomy's effectiveness for endophthalmitis, and a specific case involving a young boy with presumed sporadic inherited retinal disease.

Cytomegalovirus (CMV) infection frequently occurs after solid organ transplantation and is associated with an increased morbidity and mortality. Fortunately, the development of valganciclovir prophylaxis has lowered the incidence of CMV infection and its complications in immunosuppressed solid organ transplant recipients. However, breakthrough infections during valganciclovir prophylaxis and late CMV infection after cessation of valganciclovir prophylaxis still occur with the current prophylactic strategy. Additionally, valganciclovir resistance has emerged among CMV strains, which complicates the treatment of CMV infections. Furthermore, the use of valganciclovir is associated with myelotoxicity, which can lead to the premature withdrawal of prophylaxis. It is important to address these current issues in order to improve the standard care after solid organ transplantation. This paper will therefore discuss the clinical practice of valganciclovir prophylaxis, elaborate on its issues and suggest how to improve the current prophylactic strategy with a possible role for therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

Simple Summary: The efficacy of killing human cancer cells with a modified herpes simplex virus thymidine kinase TK.007/ganciclovir (GCV) system was investigated in malignant cells of different histogenetic origin. The aim was to determine whether different histogenetic origins of cancer cells in themselves influence their reaction towards an approach of synthetic lethality, which theoretically should be toxic in a similar range independently of the cell type. Fifteen malignant human cell lines were transduced with a lentiviral vector to stably express the TK.007 gene and cell proliferation assays under GCV. Among TK.007-expressing cell lines, lymphoma and leukemia cells were more susceptible to killing than solid cancer cells, while osteosarcoma and melanoma cells exhibited an intermediate susceptibility. This study highlights that the histogenetic origin of malignant cells strongly influences their susceptibility towards cytotoxic agents, with leukemias and lymphomas being more sensitive than solid cancer cells. Background: Remarkable differences exist in the outcome of systemic cancer therapies. Lymphomas and leukemias generally respond well to systemic chemotherapies, while solid cancers often fail. We engineered different human cancer cells lines to uniformly express a modified herpes simplex virus thymidine kinase TK.007 as a suicide gene when ganciclovir (GCV) is applied, thus in theory achieving a similar response in all cell lines. Methods: Fifteen different cell lines were engineered to express the TK.007 gene. XTT-cell proliferation assays were performed and the IC50-values were calculated. Functional kinome profiling, mRNA sequencing, and bottom-up proteomics analysis with Ingenuity pathway analysis were performed. Results: GCV potency varied among cell lines, with lymphoma and leukemia cells showing higher susceptibility than solid cancer cells. Functional kinome profiling implies a contribution of the SRC family kinases and decreased overall kinase activity. mRNA sequencing highlighted alterations in the MAPK pathways and bottom-up proteomics showed differences in apoptotic and epithelial junction signaling proteins. Conclusions: The histogenetic origin of cells influenced the susceptibility of human malignant cells towards cytotoxic agents with leukemias and lymphomas being more sensitive than solid cancer cells. [ABSTRACT FROM AUTHOR]

The article discusses the use of pre-emptive therapy (PET) and prophylaxis (PRO) for preventing cytomegalovirus (CMV) disease in liver transplant recipients. The authors compare their real-world experience with PET and PRO to the findings of a previous study. They found that PET did not significantly reduce the incidence of CMV disease compared to PRO, and PET was associated with higher costs. The authors suggest that PET may not have advantages over PRO in certain real-world settings. They also highlight the importance of carefully conducting PET according to rigorous standards for optimal efficacy. [Extracted from the article]

Cytomegalovirus (CMV) causes severe systemic and tissue-invasive disease in immunocompromised patients, particularly solid organ and hematopoietic stem cell transplant recipients. While antiviral drugs offer promising efficacy, clinical management is complicated by the high frequency of drug resistance-associated mutations. The most commonly encountered mutations occur in the genes encoding for the drug targets: UL54 (DNA polymerase), UL56 (terminase complex), and UL97 (phosphotransferase), conferring resistance to ganciclovir/cidofovir/foscarnet, letermovir, and ganciclovir/maribavir, respectively. Currently, standard practice for detecting drug resistance is sequencing-based genotypic analysis by commercial reference laboratories with strictly prescribed sample requirements and reporting parameters that can often restrict testing in a highly vulnerable population. In order to circumvent these limitations, we developed a dual-step next-generation sequencing (NGS)-based clinical assay that utilizes full-length gene amplification by long-range PCR followed by shotgun sequencing for mutation analysis. This laboratory-developed test (LDT) achieved satisfactory performance with 96.4% accuracy, 100% precision, and an analytical sensitivity of 300IU/mL with 20% allele frequency. Highlighted by two clinical cases, our NGS LDT was able to provide critical results from patient specimens with viral loads

Background: Leishmaniasis is caused by the parasite Leishmania donovani and transmitted by the bite of the sand fly vector Phlebotomus. This disease is endemic in the Bihar region of India. There are three common forms of the disease – cutaneous, mucosal and visceral leishmaniasis. The most common presentation of this disease is prolonged unexplained fever with hepatosplenomegaly. Case description: We report an unusual case of pyrexia of unknown origin (PUO) in a patient who was extensively worked up for PUO. She was found to have low CD4 counts even though serial samples were negative for HIV. Workup for PUO revealed a positive result for cytomegalovirus (CMV) IgM and polymerase chain reaction (PCR), fundoscopy suggestive of CMV retinitis and bone marrow biopsy suggestive of visceral leishmaniasis. Interestingly, there was no evidence of hepatosplenomegaly. She was diagnosed as a case of CMV infection and visceral leishmaniasis resulting in immunosuppression and was managed with parenteral ganciclovir followed by oral valganciclovir and amphotericin respectively. She had a dramatic response to the treatment and was discharged after two months of in hospital management. Conclusion: Co-infection of CMV and Leishmania in an immunocompromised patient with HIV-negative status without hepatosplenomegaly posed a diagnostic dilemma and is a rare presentation. This report shows the importance of diagnosis of this co-infectious state, which upon management with ganciclovir and amphotericin lead to resolution of symptoms and pancytopenia. Clinicians should be aware of the unusual presentation to avoid missing the diagnosis of this potentially life-threatening treatable condition.

Background/Aim: The mortality rate for alimentary tract hemorrhage remains high due to a variety of contributing factors. In this report, we present a case of postsevere trauma patient with life-threatening gastrointestinal bleeding caused by cytomegalovirus (CMV)-induced damage to the terminal ileum. Case Report: A 76-year-old female with a history of hypertension and gastrointestinal bleeding developed CMV ileitis post-severe trauma. Despite negative CMV IgM antibodies, PCR testing confirmed CMV infection in the biopsy tissue. Histopathological examination revealed viral inclusion bodies, with immunohistochemistry confirming CMV presence. Results: Intravenous ganciclovir effectively managed symptoms and halted bleeding. CMV ileitis, typically seen in immunocompromised states, may occur sporadically in immunocompetent individuals, including post-orthopedic surgery patients. The exact mechanism remains unclear, possibly related to surgical stress. Diagnosis relies on histopathology and immunohistochemistry. Conclusion: Early recognition and treatment are vital for optimal outcomes, emphasizing the need for awareness among orthopedic surgeons regarding CMV as a potential cause of postoperative complications. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection in early infancy arises more commonly as congenital infection or less commonly is acquired postnatally, although exact differentiation between both categories could be difficult. We hereby describe the case of severe CMV infection in a 2-month-old infant who was born prematurely of a twin pregnancy at 29.4 weeks. The baby presented with an array of skin manifestations comprising target lesions, papulovesicles, ulcers, and crusting along with systemic involvement (bronchopneumonia). We report this case to highlight the various unusual cutaneous manifestations of CMV infection in infancy and to raise the awareness among clinicians for the early diagnosis and prompt treatment.

Background: Extrahepatic biliary atresia (BA) is seen in infants, with an incidence of 1 in 15,000 live births. The presentation is progressive jaundice, dark-colored urine, and clay-colored stools. Kasai portoenterostomy (KPE) is the commonly performed surgical procedure in these patients. Postoperatively, phenobarbitone, ursodeoxycholic acid (UDCA), steroids, and other drugs are given to improve bile drainage and prevent inflammation and fibrosis. However, a definitive protocol regarding the need for different drugs, dosage, and duration varies across individual surgeons and centers. No universally accepted protocol exists for postoperative management after KPE. Aim: The aim of this study was to know the prevailing postoperative management of BA by subject experts and use the Delphi process to know if the experts want to change their practice based on the results from the survey. Material and Methods: A questionnaire was made after discussing with two experts in the field of BA. The questionnaire was mailed to 25 subject experts. The first survey data were analyzed and shared with all responders. In the second survey, change in the management based on the results from the first survey was assessed. Results: The Delphi questionnaire was answered by 17 experts. Postoperatively, prophylactic antibiotics are prescribed for 6–12 weeks by around 40% and >12 weeks by 30% of respondents. Phenobarbitone is prescribed for 15 KPE per year. The second survey noted that a significant percentage of responders want to change their practice according to consensus. Conclusion: From our Delphi survey, an overview of the postoperative management of BA could be made. However, multicentric studies are required for uniform protocol on the postoperative management of BA.

AIM: To report three cases of viral keratitis caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).METHODS: Slit lamp, intraocular pressure, corneal fluorescence staining, anterior segment photography, in vivo confocal microscopy(IVCM), and routine fundus screening were performed in the three confirmed patients. Treatment involved Ganciclovir, artificial tears and glucocorticoid eye drops.RESULTS: Three patients with SARS-CoV-2 keratitis(SCK)recovered well after standard treatment.CONCLUSION: SARS-CoV-2 keratitis typically presents as corneal subepithelial infiltration and can result in a decrease in corneal subepithelial nerve fiber density and an increase in dendritic cells(DC). Antiviral therapy in combination with glucocorticoid has proven to be effective.

Background: Extrahepatic biliary atresia (BA) is seen in infants, with an incidence of 1 in 15,000 live births. The presentation is progressive jaundice, dark-colored urine, and clay-colored stools. Kasai portoenterostomy (KPE) is the commonly performed surgical procedure in these patients. Postoperatively, phenobarbitone, ursodeoxycholic acid (UDCA), steroids, and other drugs are given to improve bile drainage and prevent inflammation and fibrosis. However, a definitive protocol regarding the need for different drugs, dosage, and duration varies across individual surgeons and centers. No universally accepted protocol exists for postoperative management after KPE. Aim: The aim of this study was to know the prevailing postoperative management of BA by subject experts and use the Delphi process to know if the experts want to change their practice based on the results from the survey. Material and Methods: A questionnaire was made after discussing with two experts in the field of BA. The questionnaire was mailed to 25 subject experts. The first survey data were analyzed and shared with all responders. In the second survey, change in the management based on the results from the first survey was assessed. Results: The Delphi questionnaire was answered by 17 experts. Postoperatively, prophylactic antibiotics are prescribed for 6-12 weeks by around 40% and >12 weeks by 30% of respondents. Phenobarbitone is prescribed for <3 months by nearly 50%. UDCA is prescribed for <3 months, <6 months, and 6 months-1 year by 47.1%, 23.5%, and 23.5% responders, respectively. Nearly 50% prescribe steroids (mostly prednisolone), and among them, two-thirds prescribe it for 6-12 weeks. Approximately 60% give antiviral drugs to children who are cytomegalovirus immunoglobulin M positive. In our survey, 50% of experts perform 5-10 KPE per year, and 25% each perform 10-15 and >15 KPE per year. The second survey noted that a significant percentage of responders want to change their practice according to consensus. Conclusion: From our Delphi survey, an overview of the postoperative management of BA could be made. However, multicentric studies are required for uniform protocol on the postoperative management of BA. [ABSTRACT FROM AUTHOR]

This review article describes the current knowledge about the use of antiviral chemotherapeutics in avian species, such as farm poultry and companion birds. Specific therapeutics are described in alphabetical order including classic antiviral drugs, such as acyclovir, abacavir, adefovir, amantadine, didanosine, entecavir, ganciclovir, interferon, lamivudine, penciclovir, famciclovir, oseltamivir, ribavirin, and zidovudine, repurposed drugs, such as ivermectin and nitazoxanide, which were originally used as antiparasitic drugs, and some others substances showing antiviral activity, such as ampligen, azo derivates, docosanol, fluoroarabinosylpyrimidine nucleosides, and novel peptides. Most of them have only been used for research purposes and are not widely used in clinical practice because of a lack of essential pharmacokinetic and safety data. Suggested future research directions are also highlighted. [ABSTRACT FROM AUTHOR]